Polycations have been shown to activate adenylate cyclase in beef thyroid membranes, intact adrenal and Leydig tumor cells, and in membranes derived from these tissue culture cells. The effect is due to charge-charge interactions, is biphasic, occurs with most stimulators of the enzyme (PGE, Gpp(NH)p) but not F-, does not operate directly on the $ catalytic components, and is believed due to a change in membrane conformation. Soluble thyroid membrane cyclase has been prepared to check these effects in a simpler system.